Investigations in this laboratory continue to focus on the regulatory role of lymphocytes and macrophages in connective tissue metabolism. A human continuous T lymphocyte line and human T-T hybridomas generate a factor identical to that produced by peripheral blood lymphocytes which stimulates fibroblast proliferation. This fibroblast activating factor is being isolated and characterized for the production of monoclonal antibodies. Another factor with similar activity is produced by peripheral blood monocytes isolated by counterflow centrifugal elutriation. Lymphocytes and monocytes isolated from synovium of rheumatoid arthritis patients are already activated and spontaneously generate fibroblast mitogenic factors. Such factors may mediate the overgrowth of the synovial membrane in this disease. Synovial fluid monocytes also exhibit unique chemotactic functions which may be the consequence of desensitization in an in vivo inflammatory site. Monocyte fibronectin production is enhanced in inflammation as is the ability of monocytes to generate reactive metabolites of oxygen necessary for killing of bacteria and tumor cells. Enhancement of these monocyte functions by lymphokines may influence host defense to pathogens and other inflammatory stimuli. Depletion of these mononuclear cells by leukapheresis in selected patients with rheumatoid arthritis can alleviate clinical symptoms. Furthermore, using leukapheresis as an experimental tool, it is possible to define rheumatoid arthritis as a dynamic spectrum of immunopathology with two polar extremes. Patients may have markedly suppressed T lymphocyte function, normal immune function or may comprise an intermediate group and their immunologic status correlate with histopathology and clinical responsiveness to treatment.